Project I. Experimental models of myasthenia gravis. Frogs are immunized with native and chemically modified acethylcholine receptor. Pre and postsynaptic changes in ultra-structure of the neuromuscular junction are determined. Electrophysiological studies of myasthenic junctions are designed to estimate and pre and postsynaptic contributions to the neuromusclar transmission block, and susceptibility of postsynaptic receptors to desensitization. Effect of receptor modification on antigenicity will be gauged by response of the animals. Project II. Effects of Delta9-tetrahydrocannabinol on cholinergic transmission. the action of this drug on receptor desensitization and the mechanism by which it inhjbits acetylcholine release are to be explored. Project III. Synaptic vesicle cycling. Various physiological factors which influence vesicle cycling are to be explored including certain extracellular anions, selected drugs and the effects of the tracer,horseradish peroxidase. Project IV. Cholinergic receptor desensitization. Experiments designed to test the hypothesis that the level of intracellular CA regulates receptor desensitization are to be carried out, including the actions of ruthenium red and certain catecholamines. Noise analysis is to be used in determining ion channel kinetics under various conditions which produce receptor desensitization.